Our research is directed to the study of the integrative function of gastrointestinal hormones and has focused in recent years on intestinl peptides, particularly Vasoactive Intestinal Peptide (VIP) and its homologues. We have studied the properties of natural and synthetic VIP and specific C- and N-terminal fragments. We have shown that VIP is an inhibitor of gastric secretion, a secretin-like weak stimulant of pancreatic and biliary secretion and a powerful stimulant of jejunal secretion. In addition, VIP was found to be a hyperglycemic agent, capable also of stimulating directly insulin and glucagon secretion from the pancreas. All these properties have been demonstrated in vivo as well as in vitro. Recent studies have focused on the mechanism of intestinal secretion: we have shown that VIP stimulates colonic secretion and adenylate cyclase activity. The effect of VIP occurred at physiological concentrations in the colon unlike the case in the ileum. Both secretion and enzymatic activity were blocked by lactamimide: the latter substance thus assumes a potential in the therapy of the watery diarrhea syndrome. We are currently studying the intraluminal and blood borne agents capable of releasing VIP into the circulation, the structure-activity relations of VIP and secretin utilizing fragments from the C- and N-terminal and the control by VIP of the secretion of other pancreatic and gastrointestinal hormones. BIBLIOGRAPHIC REFERENCES: Boniface, J., Picone, D., Schebalin, M., Zfass, A.M. and Makhlouf, G.M. Clearance rate, half-life and secretory potency of human gastrin-17-I in different species. Gastroenterology, In Press, 1976. Prugh, M.F., Schorr, B.A., Vlahcevic, Z.R. and Makhlouf, G.M. Intravenous pentagastrin as a partial agonist of gastric secretion in man: Evidence for the existence of hormonal inhibitory sites. Gastroenterology 68:45-49, 1975.